稳定同位素内标微透析技术用于尼古丁的药动学研究

目的:利用稳定同位素内标微透析采样技术,建立尼古丁(nicotine)经皮制剂的整体及大脑局部的药物动力学研究方法。方法:实验动物为健康大鼠,尼古丁贴剂以腹部经皮吸收的方式给药后,氘代尼古丁(DL-nicotine)作为微透析的内标物,同时进行血液及脑部的微透析采样。样品采用LC-MS/MS检测。结果:大鼠血液和脑部尼古丁的配置过程符合二室模型,其中血液的t1/2α为29.38 min,t1/2β为208.51 min,AUC0-∞为152 127.10μg.min.L-1;脑部的t1/2α为86.64 min,t1/2β为386.00 min,AUC0-∞为152 820.90μg.min.L-1;两者的tmax均为140 min。结论:氘代尼古丁可作为尼古丁的内标物进行探针回收率的校正;稳定同位素内标微透析技术可用于尼古丁经皮给药的整体和局部药动学研究,为新型给药系统的体内过程研究提供了新的思路和研究方法。

Pharmacokinetics of nicotine in blood and brain using microdialysis and stable labelled isotope

Objective: Using the stable isotopes as the internal standard of microdialysis technology to establish a new method to study the whole and local brain dynamics of nicotine percutaneous preparations.Method: Using th healthy rats as experimental animals,administrating nicotine in abdominal transdermal way,then sample in the blood and brain simultaneously by microdialysis which use deuterium nicotine(DL-nicotine) as internal standard.Detecting the samples by LC-MS/MS method.Result: The configuration process in blood and brain both conforms to 2 compartments model.t1/2 is 29.38 min,t1/2β is 208.51 min,AUC 0-∞ is 152 127.10 μg·min·L-1 in the blood t1/2 is 86.64 min,t1/2β is 386.00 min,AUC 0-∞ is 152 820.90 μg·min·L-1 in the brain.Conclusion: Dl-nicotine can be used as internal standard of nicotine to correcte the recovery;Stable isotopes internal standard microdialysis technology can be used for studing the whole and the local pharmacokinetic of nicotine and also provide new ideas and methods to studing the process of new drug delivery system.